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Simultaneous oral delivery of bioactive molecules with enhanced bioavailability is of great significance, especially when delivered from single beadlets. Here, we report the formulation, characterization, and pharmacokinetic properties of two poorly bioavailable lipophilic phytonutrients with synergistic effects, curcuminoids and 3-Acetyl-11-keto-β-boswellic acid (AKBA), following their co-delivery using fenugreek dietary fiber (Galactomannans)-based hydrogel beadlets (CGM-BSW). These beadlets are capable of extensive swelling and sustained-release of self-emulsified colloidal particles (150 – 200 nm) containing curcuminoids and AKBA allowing for improved absorption. The results of our double-blinded 4-way crossover, 4-sequence study (n = 14) demonstrated that a single dose of 250 mg of these beadlets enhanced the absorption of unconjugated curcuminoids (24.8-fold) and AKBA (6.9-fold) compared to their unformulated counterparts. The absorption of CGM-BSW formulated curcuminoids was also 5.6-fold higher than that of those formulated with turmerones (UCT). UPLC-ESI-QQQ-MS/MS was used to quantify both the curcuminoids and AKBA concentration in the plasma samples and this data was used to determine their pharmacokinetic characteristics.

Objectives: Rheumatoid factor (RF) is a well-established marker for the diagnosis and classification of rheumatoid arthritis (RA). Most studies evaluated IgM RF or isotype-nonspecific total RF assays. We evaluated the added value of IgA RF in this context., Methods: An international sample cohort consisting of samples from 398 RA patients and 1073 controls was tested for IgA RF with 3 commercial assays. For all RA patients and 100 controls essential clinical and serological data for ACR/EULAR classification were available., Results: The sensitivity of IgA RF for diagnosing RA was lower than the sensitivity of IgM RF. Differences in numerical values between IgA RF assays were observed. With all assays, the highest IgA RF values were found in patients with primary Sjögren's syndrome. Double positivity for IgM RF and IgA RF had a higher specificity for RA than either IgM RF or IgA RF. The sensitivity of double positivity was lower than the sensitivity of either IgA RF or IgM RF. Single positivity for IgA RF was at least as prevalent in controls than in RA patients. Adding IgA RF to IgM RF and anti-citrullinated protein antibodies (ACPA) did not affect RA classification. However, combined positivity for IgA RF, IgM RF and IgG ACPA had a higher specificity and lower sensitivity for RA classification than positivity for either of the antibodies., Conclusions: IgA RF showed a lower sensitivity than IgM RF. Combining IgA RF with IgM RF and ACPA did not improve sensitivity of RA classification. Combined positivity (IgA-RF/IgM-RF/ACPA) increased specificity., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

From early 2020, a high demand for SARS-CoV-2 tests was driven by several testing indications, including asymptomatic cases, resulting in the massive roll-out of PCR assays to combat the pandemic. Considering the dynamic of viral shedding during the course of infection, the demand to report cycle threshold (Ct) values rapidly emerged. As Ct values can be affected by a number of factors, we considered that harmonization of semi-quantitative PCR results across laboratories would avoid potential divergent interpretations, particularly in the absence of clinical or serological information. A proposal to harmonize reporting of test results was drafted by the National Reference Centre (NRC) UZ/KU Leuven, distinguishing four categories of positivity based on RNA copies/mL. Pre-quantified control material was shipped to 124 laboratories with instructions to setup a standard curve to define thresholds per assay. For each assay, the mean Ct value and corresponding standard deviation was calculated per target gene, for the three concentrations (10 7 , 10 5 and 10 3 copies/mL) that determine the classification. The results of 17 assays are summarized. This harmonization effort allowed to ensure that all Belgian laboratories would report positive PCR results in the same semi-quantitative manner to clinicians and to the national database which feeds contact tracing interventions.

Introduction: Commercial assays measuring antibodies to citrullinated protein/peptide (ACPA) show poor quantitative agreement. The diagnostic industry has never adopted the International Union of Immunological Societies-Centers for Disease Control and Prevention (IUIS-CDC) ACPA reference standard. Recently, the National Institute for Biological Standards and Control (NIBSC) prepared a new candidate ACPA standard (18/204). We evaluated both reference materials using different commercially available ACPA assays., Materials and Methods: This is an international study in which the NIBSC candidate ACPA standard and the IUIS-CDC ACPA reference material were analysed together with 398 diagnostic samples from individuals with rheumatoid arthritis (RA) and in 1073 individuals who did not have RA using nine commercial ACPA assays., Results: For both reference materials and samples from individuals with RA and individuals who did not have RA, there were large differences in quantitative ACPA results between assays. For most assays, values for the IUIS-CDC standard were lower than values for NIBSC 18/204 and the IUIS-CDC/NIBSC ratio was comparable for several, but not all assays. When NIBSC 18/204 was used as a calibrator, an improvement in alignment of ACPA results across several of the evaluated assays was obtained. Moreover, NIBSC 18/204 could align clinical interpretation for some but not all assays., Conclusion: Adoption of an international standard for ACPA determination is highly desirable. The candidate NIBSC 18/204 standard improved the standardisation and alignment of most ACPA assays and might therefore be recommended to be used as reference in commercial assays., Competing Interests: Competing interests: XB, LVH, GS and DS have received speaker fees from Thermo Fisher Scientific and have been a consultant for Thermo Fisher Scientific; BL and IH has received speaker fees from Thermo Fisher Scientific. All participating diagnostic companies in-kind provided the ACPA assays and provided technical training and support:Thermo Fisher Scientific, Uppsala, Sweden; Roche Diagnostics, Mannheim, Germany; Svar Life Science, Malmö, Sweden; Immunodiagnostic Systems (IDS), Tyne and Wear, United Kingdom; Orgentec, Mainz, Germany; Abbott, Wiesbaden, Germany; Euroimmun, Lübeck, Germany; Bio-Rad Laboratories, Hercules, California, USA; and Siemens Healthineers, Sudbury, United Kingdom., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are important biomarkers for diagnosis of rheumatoid arthritis (RA). However, there is poor harmonisation of RF and ACPA assays. The aim of this study was to refine RF and ACPA interpretation across commercial assays., Materials and Methods: Six total RF isotype-non-specific assays, 3 RF IgM isotype-specific assays and 9 ACPA immunoglobulin G assays of 13 different companies were evaluated using 398 diagnostic samples from patients with RA and 1073 disease controls., Results: Using cut-offs proposed by the manufacturer, there was a large variability in diagnostic sensitivity and specificity between assays. Thresholds of antibody levels were determined based on predefined specificities and used to define test result intervals. Test result interval-specific likelihood ratios (LRs) were concordant across the different RF and ACPA assays. For all assays, the LR for RA increased with increasing antibody level. Higher LRs were found for ACPA than for RF. ACPA levels associated with LRs >80 were found in a substantial fraction (>22%) of patients with RA., Conclusion: Defining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for all RF and ACPA assays., Competing Interests: Competing interests: XB, LVH, GS and DS have received speaker fees from and have been a consultant for Thermo Fisher Scientific. LBernasconi and IH have received speaker fees from Thermo Fisher Scientific. DA and PJ are editorial board members of RMD Open. All participating diagnostic companies in-kind supported with RF/ACPA assays and technical training: Thermo Fisher Scientific, Uppsala, Sweden; Cambridge Life Science, Ely, UK; Ortho-Clinical Diagnostics, Raritan, New Jersey, USA; Diagam, Ghislenghien, Belgium; Roche Diagnostics, Mannheim, Germany; Svar Life Science, Malmö, Sweden; Immunodiagnostic Systems, Tyne and Wear, UK; Orgentec, Mainz, Germany; Abbott, Wiesbaden, Germany; Euroimmun, Lübeck, Germany; Bio-Rad Laboratories, Hercules, California, USA; and Siemens Healthineers, Sudbury, UK., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients who have undergone bariatric surgery are at high risk for nutritional deficiencies before and after surgery if no proper supplementation and close follow-up are maintained. As pregnancies after these surgeries are occurring more frequently, deficiencies imply risks for both mother and child. Nutritional needs for this specific population are different from that of patients with obesity or a non-bariatric population. This review provides a comprehensive summary of the most described vitamins and minerals during pregnancy, after bariatric surgery, and during pregnancy after bariatric surgery in order to summarize their specific needs and possible side effects and to provide a useful guideline to the involved caregivers., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The prevalence of obesity is increasing globally, and along with it, there is a growing number of patients opting to undergo bariatric surgery to treat this condition. Whilst it has many advantages, bariatric surgery is known to induce micronutrient deficiency, with possible deleterious effects on overall health. This topic becomes even more relevant during pregnancy, where deficiencies can also affect the developing fetus, possibly being the cause of an increase in congenital anomalies. Most notably amongst these micronutrients is folate, or vitamin B9, which plays an essential role in development, gene expression and genomic stability. As insufficient levels of folate are associated with neural tube defects in the fetus, preventing and treating folate deficiencies during pregnancies after bariatric surgery is a relevant issue. Unfortunately, folate supplementation recommendations for bariatric patients who wish to become pregnant are not clear. In this narrative review, we discuss whether the recommendations for the general population are still valid for bariatric patients. Furthermore, we discuss the role of folate in the human body, folate status in both non-bariatric and bariatric patients, the various types of folate that are available for substitution and the risk associated with over-supplementation.

Objective: Most infections with Enterobacteriaceae producing AmpC β-lactamase (AmpC)-, extended-spectrum β-lactamase (ESBL)-, and carbapenemase-producing bacteria, vancomycin-resistant Enterococcus as well as naturally resistant non-fermenting bacteria such as Pseudomonas aeruginosa , are related to a prior colonization of the gut microbiota. The objective of this study was to determine whether treatment with probiotics during an antibiotic treatment could prevent the colonization of the gut microbiota with multi-drug resistant bacteria. Method: In total, 120 patients treated for 10 days with amoxicillin-clavulanate antibiotics were included in a randomized, placebo-controlled, double-blinded trial, comparing the effects of a 30 days treatment with placebo Saccharomyces boulardii CNCM I-745® and a probiotic mixture containing Saccharomyces boulardii, Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium lactis Bl-04, and Bifidobacterium lactis Bi-07 (Bactiol duo®). Study treatment was initiated within 48 h of the antibiotic being initiated. Most of the patients included were elderly with a mean age of 78 years old with multiple comorbidities. Stools were collected at the time of inclusion in the trial, at the end of the antibiotic treatment, and the end of the study treatment. These were cultured on selective antibiotic media. Results: Treatment with the probiotic mixture led to a significant decline in colonization with Pseudomonas after antibiotic treatment from 25 to 8.3% ( p = 0.041). Colonization with AmpC-producing enterobacteria was transiently increased after the antibiotic treatment ( p = 0.027) and declined after the probiotic intervention (p= 0.041). No significant changes were observed in the placebo and Saccharomyces groups. Up to 2 years after the trial, no infection with ESBL-producing bacteria was observed in the probiotic mixture group. Conclusion: The association of Saccharomyces boulardii with specific strains of Lactobacillus and Bifidobacterium influences antibiotic treatment by counteracting the colonization of the colon microbiota with antibiotic-resistant pathogens., Competing Interests: GW reports grants from Metagenics, during the conduct of the study. MV and GV reports non-financial support from Metagenics Europe, during the conduct of the study and an employee of Metagenics Europe, distributor of Bactiol duo used in this trial. PC is inventor on patent applications dealing with the use of A.muciniphila and its components in the treatment of obesity and related disorders and co-founder of A-Mansia biotech SA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wieërs, Verbelen, Van Den Driessche, Melnik, Vanheule, Marot and Cani.)